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CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and
D M Klinman1, A K Yi, S L Beaucage
1Section of Retroviral Immunolgy, Division of Viral Products, Food and Drug Administration, Bethesda, MD 20892-4555, USA.
Abstract:
Bacterial infection stimulates the host to mount a rapid inflammatory response. A 6-base DNA motif consisting of an unmethylated CpG dinucleotide flanked by two 5' purines and two 3' pyrimidines was shown to contribute to this response by inducing polygonal B-cell activation. This stimulatory motif is 20 times more common in the DNA of bacteria than higher vertebrates. The current work shows that the same motif induces the rapid and coordinated secretion of interleukin (IL) 6, IL-12, and interferon gamma (but not IL-2, IL-3, IL-4, IL-5, or IL-10) in vivo and in vitro. Stimulatory CpG DNA motifs induced B, T, and natural killer cells to secrete cytokine more effectively than did lipopolysaccharide. Thus, immune recognition of bacterial DNA may contribute to the cytokine, as well as the antibody production characteristic of an innate inflammatory response.
Insights
Bacterial DNA contains a specific motif that triggers immune cells like B, T, and natural killer cells to release key inflammatory cytokines. This discovery enhances our understanding of innate immune responses to bacterial infections.
Area of Science:
- Immunology
- Molecular Biology
- Microbiology
Background:
- Bacterial infections elicit rapid host inflammatory responses.
- A specific 6-base DNA motif (CpG dinucleotide flanked by purines and pyrimidines) in bacterial DNA activates B-cells.
- This motif is significantly more prevalent in bacterial DNA than in vertebrate DNA.
Purpose of the Study:
- To investigate the role of the stimulatory CpG DNA motif in inducing cytokine secretion.
- To compare the cytokine-inducing effects of CpG DNA motifs with lipopolysaccharide (LPS).
Main Methods:
- In vivo and in vitro experiments were conducted.
- The study analyzed the secretion of various interleukins (IL-6, IL-12, interferon gamma, IL-2, IL-3, IL-4, IL-5, IL-10).
- Immune cell responses (B, T, and natural killer cells) to CpG DNA motifs and LPS were assessed.
Main Results:
- The CpG DNA motif induced rapid and coordinated secretion of IL-6, IL-12, and interferon gamma.
- IL-2, IL-3, IL-4, IL-5, and IL-10 were not significantly secreted in response to the motif.
- CpG DNA motifs were more effective than LPS in stimulating cytokine secretion from B, T, and natural killer cells.
Conclusions:
- Immune recognition of bacterial DNA, specifically the CpG motif, contributes to the cytokine production characteristic of innate inflammatory responses.
- This mechanism plays a role in both cytokine and antibody production during bacterial infections.